Infectious Laryngotracheitis Virus (ILTV) is the active agent of infectious laryngotracheitis (ILT). ILT is an acute respiratory disease of poultry of global economic significance in terms of mortality and loss of egg production. The clinical symptoms of ILT can vary , and both "mild" and "severe" forms of the disease have been reported.
ILTV is a herpes virus of the alpha herpes virus subfamily. The double-stranded DNA viral genome contains approximately 160 kb pairs of DNA which has not, as yet, been fully sequenced or characterized. See generally, Kotiw et al., Avian Dis. 26:718 (1982); Leib et al., Arch. Virol. 93:287 (1987); Roizman et al., Intervirology 16:201 (1981). Previous molecular studies of the viral genome have focused largely on examining restriction endonuclease digestion patterns prepared from different field isolates of the virus. Andreasen et al., Avian Dis. 34:646 (1990); Guy et al., Avian Dis. 33:316 (1989); Kotiw et al., Avian Dis. 26:718 (1982); Kotiw et al., Vet. Microbiol. 11:319 (1986); Leib et al., Avian Dis. 30:835 (1986). In terms of sequence, the sequence of fragments of certain ILTV genes, identified through random sequencing of genomic ILTV DNA, is reported in Griffin et al., J.Gen. Vir. 70:3085 (1989). Insofar as is known, the only ILTV genes to be fully sequenced are the thymidine kinase (TK) gene, Griffin et al., J.Gen. Vir. 71:841 (1990), and the capsid p40 gene, Griffin, Nucl. Acids Res. 18:3664 (1990).
In herpesviruses, viral glycoproteins are involved in the processes of virus infection, maturation and transmission. Certain viral glycoproteins are not essential for viral growth, and are more likely related to viral tropism. Certain viral glycoproteins of ILTV have been preliminarily characterized based on molecular weight and reactivity with monoclonal antibodies. York et al., Virology 161:340 (1987). Cloning and sequencing of any full-length ILTV glycoprotein gene has not been reported.
There is evidence that herpesvirus glycoproteins are involved in interactions between the virus and the immune system of an infected host animal during the course of infection and in the development of immunity. See, for example, Glorioso et al., J. Immunol. 135:575 (1985); Roizman (ed.), The Herpesviruses, Plenum Publishing Corp: New York (1984). The gB glycoprotein of Herpes Simplex Virus, Type 1 (HSV-1) has been demonstrated to elicit both humoral and cell-mediated immune responses. Blacklaws et al., J. Gen. Virol. 68:1103 (1987); Blacklaws et al., Virology 177:727 (1990); Manservigi et al., J. Virol. 64:431 (1990); Witmer et al., J. Gen. Virol. 71:387 (1990). The sequence of the HSV-1 gB gene is disclosed in Bzik et al., Virology 133:301 (1984). The HSV-1 gB gene and other HSV-1 glycoprotein genes have been expressed using recombinant vaccinia vectors, Blacklaws et al. (1990), supra, in Bk virus episomal vectors, Manservigi et al., supra, and in adenoviral vectors, Witmer et al., supra. Expression of foreign genes in vaccinia vectors is described in U.S. Pat. Nos. 4,722,848; 4,603,112; 4,769,330; 5,017,487; 5,021,347; and 4,920,213.
The most common approach in use to immunize fowl against ILTV is the use of a live virus vaccine, or the use of infected cultured cells, as disclosed, for example in U.S. Pat. No. 4,980,162 to Honda et al. Live vaccines are not always effective, however, and can be pathogenic even if prepared from low-virulence field isolates.
In the art, viral proteins including viral envelope glycoproteins have been used to prepare subunit vaccines. Subunit vaccines are considered to be a safer alternative in that such vaccines contain no live virus and no viral genetic material. Depending on how it is produced, the viral subunit may or may not be glycosylated. Subunit vaccines based on the HSV gB glycoprotein are disclosed in U.S. Pat. Nos. 4,724,146; 4,661,349; and 4,642,333.
Homologs of the HSV-1 gB gene have been found in a number of different herpesviruses, including pseudorabies virus (PRV), Marek's disease virus (MDV), Varicella zoster virus (VZV), bovine herpes virus type 1 (BHV-1), equine herpesvirus 4 (EHV-4), human cytomegalovirus (HCMV), and Epstein Barr Virus (EBV).